This product is a CRISPR/Cas9-edited polyclonal knockout cell population of the 769-P human renal cell adenocarcinoma line with targeted disruption of the BAG3 gene. The polyclonal format provides a heterogeneous pool of gene-edited cells, enabling functional loss-of-function studies without clonal selection bias. BAG3 knockout eliminates the stress-inducible co-chaperone, making it an essential tool for investigating BAG3-dependent processes.
The 769-P cell line originates from a primary clear cell renal carcinoma and provides a robust in vitro model of clear cell renal cell carcinoma (ccRCC), the most common kidney cancer subtype. These adherent epithelial cells maintain key genetic alterations, including VHL loss, and exhibit characteristic signaling pathway activation, rendering them an appropriate platform for investigating ccRCC biology, drug sensitivity, and pathway-targeted interventions.
BAG3 is a stress-inducible co-chaperone central to proteostasis. It forms complexes with HSP70 and HSPB8, escorting ubiquitinated misfolded proteins to autophagosomes through interactions with p62/SQSTM1 and LC3, promoting LC3-II lipidation. Concurrently, BAG3 stabilizes Bcl-2, inhibiting BAX oligomerization and caspase-3 cleavage. Upstream regulators including heat shock factor 1 (HSF1), NF-??B, and STAT3 drive BAG3 transcription in response to proteotoxic and oncogenic stress, integrating chaperone-mediated autophagy and anti-apoptotic signaling.
In ccRCC, BAG3 overexpression correlates with advanced disease and therapy resistance. The 769-P BAG3 knockout model enables systematic evaluation of BAG3-dependent autophagy flux and apoptosis thresholds. Abrogating BAG3 can impair clearance of ubiquitinated aggregates, promote mitochondrial apoptosis, and sensitize cells to proteasome inhibitors (bortezomib) or platinum chemotherapeutics (cisplatin), highlighting its role in maintaining oncogenic fitness under therapeutic stress.
This polyclonal knockout cell pool supports a broad range of applications, including autophagy monitoring via LC3-II turnover and p62 degradation kinetics, immunofluorescence visualization of autophagic structures, co-immunoprecipitation of HSP70-BAG3 complexes, caspase-3/7 activation profiling, and Transwell migration/invasion assays. Drug dose-response studies with bortezomib, cisplatin, or other agents can clarify BAG3??s contribution to chemoresistance. For further details or custom requests, please contact Ascent Research.
